Dihydroxyacetone phosphate accumulation leads to podocyte pyroptosis in diabetic kidney disease.

Diabetic kidney disease (DKD) can lead to accumulation of glucose upstream metabolites due to dysfunctional glycolysis. But the effects of accumulated glycolysis metabolites on podocytes in DKD remain unknown. The present study examined the effect of dihydroxyacetone phosphate (DHAP) on high glucose induced podocyte pyroptosis. By metabolomics, levels of DHAP, GAP, glucose-6-phosphate and fructose 1, 6-bisphosphate were significantly increased in glomeruli of db/db mice. Furthermore, the expression of LDHA and PKM2 were decreased. mRNA sequencing showed upregulation of pyroptosis-related genes (Nlrp3, Casp1, etc.). Targeted metabolomics demonstrated higher level of DHAP in HG-treated podocytes. In vitro, ALDOB expression in HG-treated podocytes was significantly increased. siALDOB-transfected podocytes showed less DHAP level, mTORC1 activation, reactive oxygen species (ROS) production, and pyroptosis, while overexpression of ALDOB had opposite effects. Furthermore, GAP had no effect on mTORC1 activation, and mTORC1 inhibitor rapamycin alleviated ROS production and pyroptosis in HG-stimulated podocytes. Our findings demonstrate that DHAP represents a critical metabolic product for pyroptosis in HG-stimulated podocytes through regulation of mTORC1 pathway. In addition, the results provide evidence that podocyte injury in DKD may be treated by reducing DHAP.

Effect of ionic groups on the morphology and transport properties in a novel perfluorinated ionomer containing sulfonic and phosphonic acid groups: a molecular dynamics study.

Combining the phosphonic acid group with the sulfonic acid group in PEMs has been shown to be an effective strategy for improving the fuel cell performance. However, the interplay of two different ionic groups and the resulting effect on the membrane properties have not been fully elucidated. Here, we used classical molecular dynamics simulation to investigate the morphologies, transport properties and effects of ionic groups in a novel perfluorinated PEM containing two ionic groups (PFSA-PFPA) in comparison to the corresponding homopolymers. Phase separations between hydrophilic and hydrophobic domains are confirmed in these PEMs and result from the evolution of water clusters formed around the ionic groups. The combination of both ionic groups brings a complicated morphological feature in PFSA-PFPA, with near-cylindrical aqueous domains of large length scales interconnected by tortuous domains of small sizes. And we found that the self-diffusion coefficients of water molecules are strongly related to morphologies, with the water transport in PFSA-PFPA lying between two analogous homopolymers. At the molecular level, we found that the sulfonic and phosphonic acid groups have distinct effects on the coordination behaviors and the dynamics of water molecules and hydronium ions. Strong electrostatic interactions lead to compact coordination structures and sluggish dynamics of hydronium ions around phosphonic acid groups, which determine the morphological evolution and transport properties in PFSA-PFPA. Our study affords insights into the relationship between molecular characteristics and transport properties bridged by phase-separated morphologies in a novel PEM containing both sulfonic acid and phosphonic acid groups, which deepens the understanding of the interplay between two ionic groups and may inspire the rational design of high-performance PEMs.

Reduction of anaerobic glycolysis contributes to angiotensin II-induced podocyte injury with foot process effacement.

Activation of the renin-angiotensin system is associated with podocyte injury and has been well demonstrated as a pivotal factor in the progression of chronic kidney disease. Podocyte energy metabolism is crucial for maintaining their physiological functions. However, whether renin-angiotensin system activation promotes chronic kidney disease progression by disturbing the energy metabolism of podocytes has not been elucidated. Angiotensin II, the main active molecule of the renin-angiotensin system, plays a crucial role in chronic kidney disease initiation and progression, but its impact on podocyte metabolism remains unclear. Here, we demonstrate a rapid decrease in the expression of pyruvate kinase M2, a key glycolytic enzyme, and reduced glycolytic flux in podocytes exposed to angiotensin II in vivo and in vitro. Podocyte-specific deletion of pyruvate kinase M2 in mice aggravated angiotensin II-induced glomerular and podocyte injury with foot process effacement and proteinuria. The inhibition of glycolysis was accompanied by adenosine triphosphate deficiency, cytoskeletal remodeling and podocyte apoptosis. Mechanistically, we found that angiotensin II-induced glycolysis impairment contributed to an insufficient energy supply to the foot process, leading to podocyte injury. Additionally, pyruvate kinase M2 expression was found to be reduced in podocytes from kidney biopsies of patients with hypertensive nephropathy and diabetic kidney disease. Thus, our findings suggest that glycolysis activation is a potential therapeutic strategy for podocyte injury.

Development of Ruthenium Nanophotocages with Red or Near-Infrared Light-Responsiveness.

The development of light-triggered ruthenium (Ru) nanophotocages has revolutionized conventional methods of drug administration, thereby facilitating cancer therapy in a noninvasive and temperate manner. Ru nanophotocages employ a distinct approach known as photoactivated chemotherapy (PACT), wherein light-induced ligand dissociation yields a toxic metal complex or a ligand capable of performing other functions such as optically controlled protein degradation and drug delivery. Simultaneously, this process is accompanied by the generation of reactive oxygen species (ROS), which serve as an effective anticancer agent in combination with PACT and photodynamic therapy (PDT). Due to its exceptional attributes of extended tissue penetration, and minimized tissue damage, red light or near-infrared light is widely acknowledged as the "phototherapeutic window" (650-900 nm). In this Concept, we present an overview of the most recent advancements in Ru nanophotocages within the phototherapeutic range. Diverse aspects, including design principles, photocaging efficacy, photoactivation mechanisms, and potential applications in the field of biomedical chemistry, are discussed. Questions and challenges regarding their synthesis, characterization, and applications are also discussed. This Concept would foster further exploration into the realm of Ru nanophotocages.

Targeted co-delivery of curcumin and erlotinib by MoS2 nanosheets for the combination of synergetic chemotherapy and photothermal therapy of lung cancer.

BACKGROUND: Curcumin (Cur), a bioactive component of Chinese traditional medicine, has demonstrated inhibitory properties against cancer cell proliferation while synergistically enhancing the anticancer efficacy of erlotinib (Er). However, the individual limitations of both drugs, including poor aqueous solubility, lack of targeting ability, short half-life, etc., and their distinct pharmacokinetic profiles mitigate or eliminate their combined antitumor potential. RESULTS: In this study, we developed a molybdenum disulfide (MoS2)-based delivery system, functionalized with polyethylene glycol (PEG) and biotin, and co-loaded with Cur and Er, to achieve efficient cancer therapy. The MoS2-PEG-Biotin-Cur/Er system effectively converted near-infrared (NIR) light into heat, thereby inducing direct photothermal ablation of cancer cells and promoting controlled release of Cur and Er. Biotin-mediated tumor targeting facilitated the selective accumulation of MoS2-PEG-Biotin-Cur/Er at the tumor site, thus enhancing the synergistic antitumor effects of Cur and Er. Remarkably, MoS2-PEG-Biotin-Cur/Er achieved the combination of synergistic chemotherapy and photothermal therapy (PTT) upon NIR irradiation, effectively suppressing lung cancer cell proliferation and inhabiting tumor growth in vivo. CONCLUSIONS: The as-synthesized MoS2-PEG-Biotin-Cur/Er, featuring high targeting ability, NIR light-responsive drug release, and the integration of synergistic chemotherapy and PTT, may provide a promising strategy for the treatment of lung cancer in clinical practice.

PFKFB3 downregulation aggravates Angiotensin II-induced podocyte detachment.

Podocytes play a critical role in maintaining normal glomerular filtration, and podocyte loss from the glomerular basement membrane (GBM) initiates and worsens chronic kidney disease (CKD). However, the exact mechanism underlying podocyte loss remains unclear. Fructose-2,6-biphosphatase 3 (PFKFB3) is a bifunctional enzyme that plays crucial roles in glycolysis, cell proliferation, cell survival, and cell adhesion. This study aimed to determine the role of PFKFB3 in angiotensin II (Ang II) kidney damage. We found that mice infused with Ang II developed glomerular podocyte detachment and impaired renal function accompanied by decreased PFKFB3 expression in vivo and in vitro. Inhibition of PFKFB3 with the PFKFB3 inhibitor 3PO further aggravated podocyte loss induced by Ang II. In contrast, activating PFKFB3 with the PFKFB3 agonist meclizine alleviated the podocyte loss induced by Ang II. Mechanistically, PFKFB3 knockdown likely aggravate Ang II-induced podocyte loss by suppressing talin1 phosphorylation and integrin beta1 subunit (ITGB1) activity. Conversely, PFKFB3 overexpression protected against Ang II-induced podocyte loss. These findings suggest that Ang II leads to a decrease in podocyte adhesion by suppressing PFKFB3 expression, and indicates a potential therapeutic target for podocyte injury in CKD.

Zintl-phase Eu2ZnSb2: A promising thermoelectric material with ultralow thermal conductivity.

Zintl compounds are considered to be potential thermoelectric materials due to their "phonon glass electron crystal" (PGEC) structure. A promising Zintl-phase thermoelectric material, 2-1-2-type Eu2ZnSb2 (P63/mmc), was prepared and investigated. The extremely low lattice thermal conductivity is attributed to the external Eu atomic layers inserted in the [Zn2Sb2]2- network in the structure of 1-2-2-type EuZn2Sb2 [Formula: see text], as well as the abundant inversion domain boundary. By regulating the Zn deficiency, the electrical properties are significantly enhanced, and the maximum ZT value reaches ∼1.0 at 823 K for Eu2Zn0.98Sb2 Our discovery provides a class of Zintl thermoelectric materials applicable in the medium-temperature range.

Tripping Avoidance Lower Extremity Exoskeleton Based on Virtual Potential Field for Elderly People.

Tripping is a common problem that everyone faces when walking. This paper mainly focuses on a lower limb exoskeleton that can help those weak in joints to avoid tripping when negotiating stairs or stepping over obstacles. This method does not need a camera or map reconstruction to recognize the obstacles and plan paths. The exoskeleton applies an impedance controller to follow and control the pilot's movements. A virtual potential field is proposed to help the robot regulate the pilot's motion and avoid kicking the obstacles appearing in front of the pilot's foot during walking. Simulation and experiments show that this method works effectively and could help the elderly and those affected by joint weakness avoid tripping when walking.

Optical sensors using chaotic correlation fiber loop ring down.

We have proposed a novel optical sensor scheme based on chaotic correlation fiber loop ring down (CCFLRD). In contrast to the well-known FLRD spectroscopy, where pulsed laser is injected to fiber loop and ring down time is measured, the proposed CCFLRD uses a chaotic laser to drive a fiber loop and measures autocorrelation coefficient ring down time of chaotic laser. The fundamental difference enables us to avoid using long fiber loop as required in pulsed FLRD, and thus generates higher sensitivity. A strain sensor has been developed to validate the CCFLRD concept. Theoretical and experiment results demonstrate that the proposed method is able to enhance sensitivity by more than two orders of magnitude comparing to the existing FLRD method. We believe the proposed method could find great potential applications for chemical, medical, and physical sensing.

Thickened Perirenal Fat Predicts Poor Renal Outcome in Patients with Immunoglobulin A Nephropathy: A Population-Based Retrospective Cohort Study.

Introduction: Perirenal fat is a pad that fills the retroperitoneal space outside the kidney, which affects kidney function in various ways. However, the association between perirenal fat and IgA nephropathy (IgAN) has not yet been elucidated. This study aimed to investigate the role of perirenal fat in predicting IgAN progression. Methods: A total of 473 patients with biopsy-proven IgAN and follow-up information were recruited, and perirenal fat thickness (PFT) was measured using color Doppler ultrasonography at renal biopsy. Patients were divided into two groups according to the median PFT: the low-PFT group (PFT ≤1.34 cm, n = 239) and the high PFT group (PFT >1.35 cm, n = 234). A total of 473 healthy participants were included in the control group. Basic clinical characteristics were assessed at the time of renal biopsy, and the relationship between PFT and combined endpoints was analyzed. The renal composite endpoints were defined as a two-fold increase in blood creatinine level, end-stage renal disease (dialysis over 3 months). Kaplan-Meier survival analysis was used to explore the role of PFT in the progression of IgAN. Three clinicopathological models of multivariate Cox regression analysis were established to evaluate the association between PFT and renal prognosis in patients with IgAN. Results: Compared to healthy subjects, patients with IgAN showed significantly higher PFT. After a median follow-up of 50 months, 75 of 473 patients (15.9%) with IgAN reached renal composite endpoints. Among those, 13 of 239 patients (5.4%) were in the low PFT group, and 62 of 234 patients (26.5%) were in the high PFT group (p < 0.001). The results of three Cox regression models (including demographics, pathological and clinical indicators, and PFT) demonstrated that a higher PFT was significantly associated with a higher risk of reaching renal composite endpoints in patients with IgAN. Conclusion: This study indicated a positive relationship between PFT at renal biopsy and renal progression in patients with IgAN, suggesting that perirenal fat might act as a marker of poor prognosis in patients with IgAN.

Blockade of STARD3-mediated cholesterol transport alleviates diabetes-induced podocyte injury by reducing mitochondrial cholesterol accumulation.

AIMS: Steroidogenic acute regulatory (StAR)-related lipid transfer domain-3 (STARD3) is a sterol-binding protein that facilitates cholesterol transport between cellular organelles. Cholesterol accumulation in podocytes directly contributes to the pathogenesis of albuminuria and renal injury under the condition of diabetic kidney disease (DKD). The aim of this study is to determine the role of STARD3 on the intracellular distribution of cholesterol within podocytes. METHODS: In vivo and in vitro models of diabetes were performed. The protein levels of STARD3, Niemann-Pick disease type C1 (NPC1), and Niemann-Pick disease type C2 (NPC2) were respectively detected by western blot analysis, immunohistochemistry, and immunofluorescence. Filipin staining was used to evaluate the subcellular localization of cholesterol in podocytes. Mitochondrial damage was evaluated using JC-1 (CBIC2) and ROS (reactive oxygen species) assays. KEY FINDINGS: Upregulation of STARD3 under diabetes and hyperglycemia increases cholesterol transport from the late endosomal/lysosomal (LE/LY) to mitochondria, leading to mitochondrial cholesterol accumulation and cell injury in podocytes. Conversely, downregulating STARD3 expression attenuated mitochondrial cholesterol accumulation, and improved mitochondrial homeostasis. SIGNIFICANCE: STARD3 may govern intracellular cholesterol transport in podocytes, subsequently leading to regulation of mitochondrial metabolism. Therefore, targeting STARD3 emerges as a potential therapeutic strategy to mitigate diabetes-induced mitochondrial cholesterol accumulation and associated injury in podocytes.

Improved Thermoelectric Performance of p-Type PbTe by Entropy Engineering and Temperature-Dependent Precipitates.

Entropy engineering is aneffective scheme to reduce the thermal conductivity of thermoelectric materials, but it inevitably deteriorates the carrier mobility. Here, we report the optimization of thermoelectric performance of PbTe by combining entropy engineering and nanoprecipitates. In the continuously tuned compounds of Pb0.98Na0.02Te(1-2x)SxSex, we show that the x = 0.05 sample exhibits an exceptionally low thermal conductivity relative to its configuration entropy. By introducing Mn doping, the produced temperature-dependent nanoprecipitates of MnSe cause the high-temperature thermal conductivity to be further reduced. A very low lattice thermal conductivity of 0.38 W m-1 K-1 is achieved at 825 K. Meanwhile, the carrier mobility of the samples is only slightly influenced, owing to the well-controlled configuration entropy and the size of nanoprecipitates. Finally, a high peak zT of ∼2.1 at 825 K is obtained in the Pb0.9Na0.04Mn0.06Te0.9S0.05Se0.05 alloy.

ESRRA modulation by empagliflozin mitigates diabetic tubular injury via mitochondrial restoration.

BACKGROUND: The protection of the diabetic kidney by Empagliflozin (EMPA) is attributed to its interaction with the sodium glucose cotransporter 2 located on proximal tubular epithelial cells (PTECs). Estrogen-related receptor α (ESRRA), known for its high expression in PTECs and association with mitochondrial biogenesis, plays a crucial role in this process. This study aimed to explore the impact of ESRRA on mitochondrial mass in diabetic tubular injury and elucidate the mechanism underlying the protective effects of EMPA. METHODS: Mitochondrial changes in PTECs of 16-week-old diabetic mice were assessed using transmission electron microscopy (TEM) and RNA-sequences. In vivo, EMPA administration was carried out in db/db mice for 8 weeks, while in vitro experiments involved modifying ESRRA expression in HK2 cells using pcDNA-ESRRA or EMPA. RESULTS: Evaluation through TEM revealed reduced mitochondrial mass and swollen mitochondria in PTECs, whereas no significant changes were observed under light microscopy. Analysis of RNA-sequences identified 110 downregulated genes, including Esrra, associated with mitochondrial function. Notably, ESRRA overexpression rescued the loss of mitochondrial mass induced by high glucose (HG) in HK2 cells. EMPA treatment ameliorated the ultrastructural alterations and mitigated the downregulation of ESRRA both in db/db mice and HG-treated HK2 cells. CONCLUSION: The diminished expression of ESRRA is implicated in the decline of mitochondrial mass in PTECs during the early stages of diabetes, highlighting it as a key target of EMPA for preventing the progression of diabetic kidney injury.

CALPHAD accelerated design of advanced full-Zintl thermoelectric device.

Since thermoelectric materials have different physical and chemical properties, the design of contact layers requires dedicated efforts, and the welding temperatures are distinctly different. Therefore, a general interface design and connection technology can greatly facilitate the development of thermoelectric devices. Herein, we proposed a screening strategy for the contact materials based on the calculation of phase diagram method, and Mg2Ni has been identified as a matched contact layer for n-type Mg3Sb2-based materials. And this screening strategy can be effectively applied to other thermoelectric materials. By adopting the low-temperature sintering silver nanoparticles technology, the Zintl phase thermoelectric device can be fabricated at low temperature but operate at medium temperature. The single-leg n-type Mg3.15Co0.05SbBi0.99Se0.01 device achieves an efficiency of ~13.3%, and a high efficiency of ~11% at the temperature difference of 430 K has been realized for the Zintl phase thermoelectric device comprised together with p-type Yb0.9Mg0.9Zn1.198Ag0.002Sb2. Additionally, the thermal aging and thermal cycle experiments proved the long-term reliability of the Mg2Ni/Mg3.15Co0.05SbBi0.99Se0.01 interface and the nano-silver sintering joints. Our work paves an effective avenue for the development of advanced devices for thermoelectric power generation.

STING contributes to lipopolysaccharide-induced tubular cell inflammation and pyroptosis by activating endoplasmic reticulum stress in acute kidney injury.

Recently, innate immunity and inflammation were recognized as the key factors for acute kidney injury (AKI) caused by sepsis, which is closely related to high mortality. Stimulator of interferon genes (STING) has emerged as a critical component of innate immune and inflammatory responses. However, the role of STING in the pathogenesis of septic AKI remains unclear. This study demonstrated that the STING was significantly activated in tubular cells induced by lipopolysaccharide (LPS) in vivo and in vitro. Tubule-specific STING knockout attenuated LPS-induced renal dysfunction and pathological changes. Mechanistically, the STING pathway promotes NOD-like receptor protein 3 (NLRP3) activation. STING triggers endoplasmic reticulum (ER) stress to induce mitochondrial reactive oxygen species (mtROS) overproduction, enhancing thioredoxin-interacting protein activation and association with NLRP3. Eventually, the NLRP3 inflammasome leads to tubular cell inflammation and pyroptosis. This study revealed the STING-regulated network and further identified the STING/ER stress/mtROS/NLRP3 inflammasome axis as an emerging pathway contributing to tubular damage in LPS-induced AKI. Hence, targeting STING may be a promising therapeutic strategy for preventing septic AKI.

Bi2Te3-Based Thermoelectric Modules for Efficient and Reliable Low-Grade Heat Recovery.

Bismuth-telluride-based alloy has long been considered as the most promising candidate for low-grade waste heat power generation. However, optimizing the thermoelectric performance of n-type Bi2Te3 is more challenging than that of p-type counterparts due to its greater sensitivity to texture, and thus limits the advancement of thermoelectric modules. Herein, the thermoelectric performance of n-type Bi2Te3 is enhanced by incorporating a small amount of CuGaTe2, resulting in a peak ZT of 1.25 and a distinguished average ZT of 1.02 (300-500 K). The decomposed Cu+ strengthens interlayer interaction, while Ga+ optimizes carrier concentration within an appropriate range. Simultaneously, the emerged numerous defects, such as small-angle grain boundaries, twin boundaries, and dislocations, significantly suppresses the lattice thermal conductivity. Based on the size optimization by finite element modelling, the constructed thermoelectric module yields a high conversion efficiency of 6.9% and output power density of 0.31 W cm-2 under a temperature gradient of 200 K. Even more crucially, the efficiency and output power little loss after subjecting the module to 40 thermal cycles lasting for 6 days. This study demonstrates the efficient and reliable Bi2Te3-based thermoelectric modules for broad applications in low-grade heat harvest.

LRH-1 activation alleviates diabetes-induced podocyte injury by promoting GLS2-mediated glutaminolysis.

Alteration of metabolic phenotype in podocytes directly contributes to the development of albuminuria and renal injury in conditions of diabetic kidney disease (DKD). This study aimed to identify and evaluate liver receptor homologue-1 (LRH-1) as a possible therapeutic target that alleviates glutamine (Gln) metabolism disorders and mitigates podocyte injury in DKD. Metabolomic and transcriptomic analyses were performed to characterize amino acid metabolism changes in the glomeruli of diabetic mice. Next, Western blotting, immunohistochemistry assays, and immunofluorescence staining were used to detect the expression of different genes in vitro and in vivo. Furthermore, Gln and glutamate (Glu) content as well as ATP generation were examined. A decrease in LRH-1 and glutaminase 2 (GLS2) expression was detected in diabetic podocytes. Conversely, the administration of LRH-1 agonist (DLPC) upregulated the expression of GLS2 and promoted glutaminolysis, with an improvement in mitochondrial dysfunction and less apoptosis in podocytes compared to those in vehicle-treated db/db mice. Our study indicates the essential role of LRH-1 in governing the Gln metabolism of podocytes, targeting LRH-1 could restore podocytes from diabetes-induced disturbed glutaminolysis in mitochondria.

STING deletion alleviates podocyte injury through suppressing inflammation by targeting NLRP3 in diabetic kidney disease.

An increasing number of studies have shown that immune inflammatory response plays a vital role in diabetic kidney disease (DKD). Nod-like receptor protein 3 (NLRP3) inflammasome-dependent inflammatory response is a key mechanism in the initiation and development of DKD. The stimulator of interferon genes (STING) is an adaptor protein that can drive noninfectious inflammation and pyroptosis. However, the mechanism of STING regulating immune inflammation and the interaction with NLRP3-dependent pyroptosis in high glucose state still remains unclear. This study evaluated the potential role of STING in high glucose (HG)-induced podocyte inflammation response. STING expression was significantly increased in db/db mice, STZ-treated diabetic mice, and HG-treated podocytes. Podocyte-specific deletion of STING alleviated podocyte injury, renal dysfunction, and inflammation in STZ-induced diabetic mice. STING inhibitor (H151) administration ameliorated inflammation and improved renal function in db/db mice. STING deletion in podocytes attenuated the activation of the NLRP3 inflammasome and podocyte pyroptosis in STZ-induced diabetic mice. In vitro, modulated STING expression by STING siRNA alleviated pyroptosis and NLRP3 inflammasome activation in HG-treated podocytes. NLRP3 over-expression offset the beneficial effects of STING deletion. These results indicate that STING deletion suppresses podocyte inflammation response through suppressing NLRP3 inflammasome activation and provide evidence that STING may be a potential target for podocyte injury in DKD.

Optimized Thermoelectric Cooler Performance by the Structure-Matching Design of Asymmetrical p/n-Type Legs.

Commercial Bi2Te3-based thermoelectric (TE) coolers typically comprise equal-size p- and n-type legs. However, this traditional structure limits the cooling temperature differences of TE coolers (TECs) due to identical current density, when their electrical or thermal characteristics differ significantly. This work presents a novel design of p- and n-type TE legs to optimize the performance of TECs. The cooling properties of the materials are initially calculated by theoretical equations and then evaluated by using a combination of finite element simulations and experiments. The research findings suggest that by utilizing higher ZT p-type materials to enhance the TEC cooling performance, further optimization of the ratio of the cross-sectional area of the TE legs (Ap/An) improves the structural matching of the legs, which achieves the maximum figure of merit Z and leads to a 5.4% increase in cooling power density. Additionally, the TEC with optimized Ap/An increases the cooling temperature difference by 3.3 and 2.7 K for the same current at hot side temperatures of 300 and 315 K, respectively, while the coefficient of performance remains unchanged. Moreover, the maximum cooling temperature difference reaches 70 and 74 K, respectively. We anticipate that our results will guide the design and optimization of the TECs.

SIRT6 Activator UBCS039 Inhibits Thioacetamide-Induced Hepatic Injury In Vitro and In Vivo.

SIRT6 has been reported to have multiple functions in inflammation and metabolism. In the present study, we explored the regulatory effects and mechanisms of SIRT6 in thioacetamide (TAA)-induced mice acute liver failure (ALF) models. The SIRT6 activator UBCS039 was used in this animal and cell experiments. We observed that UBCS039 ameliorated liver damage, including inflammatory responses and oxidative stress. Further study of mechanisms showed that the upregulation of SIRT6 inhibited the inflammation reaction by suppressing the nuclear factor-κB (NF-κB) pathway in the TAA-induced ALF mice model and lipopolysaccharide-stimulated macrophages. In addition, the upregulation of SIRT6 alleviated oxidative stress damage in hepatocytes by regulating the Nrf2/HO-1 pathway. These findings demonstrate that pharmacologic activator of SIRT6 could be a promising target for ALF.